Dexmedetomidine impairs P-glycoprotein-mediated efflux function in L02 cells via the adenosine 5′-monophosphate-activated protein kinase/nuclear factor-κB pathway

نویسندگان

  • Guo-Rong He
  • Xiao-Kun Lin
  • Yong-Biao Wang
  • Cong-De Chen
چکیده

Dexmedetomidine (DEX) a type of the anaesthetic that has been widely used in anaesthesia and intensive care. However, whether DEX affects the pharmacokinetics of drugs remains elusive. As hepatic P‑glycoprotein (P‑gp) serves a critical role in the disposition of drugs, the present study aimed to address whether P‑gp function could be affected by DEX in vitro. In the present study, L02 cells (a normal human liver cell line) were exposed to DEX for 24 h and P‑gp function was evaluated by the intracellular accumulation of Rhodamine 123. The results indicated that P‑gp function was significantly impaired by DEX treatment and that the mRNA levels and protein levels of P‑gp were downregulated in a dose‑ and time‑dependent manner. Importantly, DEX‑induced downregulation of P‑gp was associated with adenosine 5'‑monophosphate-activated protein kinase (AMPK) activation, as it was significantly attenuated by AMPK inhibition using dorsomorphin. Furthermore, the results revealed that changes in the subcellular localisation of nuclear factor (NF)‑κB following AMPK activation were involved in the P‑gp regulation in response to DEX treatment. Collectively, these results suggested that DEX impairs P-glycoprotein‑mediated efflux function in L02 cells via the AMPK/NF‑κB pathway, which provided direct evidence that the hepatic disposition of drugs may be affected by DEX through the downregulation of P‑gp.

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عنوان ژورنال:

دوره 17  شماره 

صفحات  -

تاریخ انتشار 2018